The gut microbiota plays a key role in metabolism and immune regulation, and imbalance in microbial composition can contribute to various diseases. We present up-to-date data on the role of the gut microbiota in the occurrence of chronic hyperuricemia (HU) and gout, which is associated with the influence of the microbiota on the synthesis of purine-metabolizing enzymes and pro-inflammatory cytokines. It has been shown that the gut microbiota plays an important role in the pathophysiology of gout and can serve as a new target for therapy. Currently, the microbial index of gout is considered as a potential method for early diagnosis of the disease, possibly already at the preclinical stage. The gut microbiota can be a starting point in the study of the pathogenesis of HU and gout. This makes it necessary to assess the pathogenetic relationship between individual specific microorganisms, the microbiota as a whole, and the development of uric acid (UA) metabolism disorders that contribute to the onset of HU and its transformation into gout. It is assumed that this approach will provide a more complete understanding of the gut microbiota participation in the synthesis of UA and its extrarenal excretion, as well as of bacteria and bacterial enzymes that can be used as a probiotic coadjuvant for the treatment and prevention of gout.

Objective: to identify clinical and immunological variants (phenotypes) of systemic lupus erythematosus (SLE) using cluster analysis.

Patients and methods. The study included 400 patients with diagnosis of SLE according to the 2012 SLICC classification criteria. Patients underwent laboratory and immunological workup according to accepted standards of medical care for patients with SLE, and therapy was prescribed in accordance with disease activity.

Results and discussion. Among patients, most were females (ratio of men and women – 1:10), and people of young age (34.2±11.5 years), with an average duration of illness of 6 [3; 12] years. In 98 (25%) patients with SLE, the disease debuted before the age of 18 years. Lupus nephritis (LN) was detected in 192 (48%) patients, SLE with antiphospholipid syndrome (APS) – in 48 (12%), SLE with Sjцgren's syndrome – in 44 (11%). For cluster analysis 30 clinical, 4 laboratory, 12 immunological and 10 therapeutic parameters were selected and a dendrogram was constructed with the calculation of the Euclidean distance using the Ward method. As a result, five clusters of SLE were identified: with the development of LN; with predominantly extrarenal manifestations; SLE combined with APS; SLE combined with Sjцgren's syndrome; SLE with a debut in childhood (up to 18 years of age). Clusters differed in clinical, laboratory and immunological parameters, as well as in therapy.

Conclusion. Cluster analysis data made it possible to group the selected signs into five clinical and immunological variants (phenotypes) of SLE. Identification of SLE phenotypes as a set of characteristics that, individually or in combination, make it possible to determine differences between patients based on clinical, laboratory and immunological parameters, variants of the onset and course of the disease, response to therapy and prognosis, will contribute to a personalized approach in choosing the therapy, improving its long-term results, as well as quality of life and prognosis in patients with SLE.

The effectiveness of personalized therapy for rheumatoid arthritis (RA) is associated with the correct choice of the drug and the ability to predict its effect before starting the treatment.

Objective: to study in patients with RA the relationship between results of therapy and initial expression of genes responsible for bone and articular cartilage resorption (matrix metalloproteinase 9 – MMP9, – cathepsin K) and inflammation (tumor necrosis factor α – TNFα – and interleukin 1β – IL1β) in mononuclear cells of peripheral blood (PBMC), cultured with tofacitinib (TOFA).

Patients and methods. We examined 12 patients with RA who had not previously received TOFA. The average age of the patients was 51 years, the average duration of the disease was 37.6 months. After 3 months of TOFA therapy, 6 patients achieved remission, while the rest had high and moderate disease activity. PBMC were isolated before therapy using a Ficoll density gradient and cultured in the presence of 100 nM TOFA for 48 h. Total RNA obtained from these cells was used to analyze the expression of MMP9, cathepsin K, IL1β, and TNFα genes using a real-time quantitative reverse transcription polymerase chain reaction.

Results and discussion. TOFA is able to modify gene expression in cultured PBMC from RA patients compared to control cells. The initial expression of all the studied genes was significantly increased in cultured with TOFA cells of patients with persistent high and moderate disease activity during therapy, while TNFα gene expression was significantly reduced in patients who achieved remission.

Conclusion. In patients with RA who have not previously received TOFA, a decrease in TNFα gene expression in blood cells cultured with this drug before the start of therapy may be a prognostic biomarker for achieving remission during TOFA therapy. 

Objective: to study the clinical and economic aspects of the use of biological disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), Janus kinase inhibitors (JAKi), for the treatment of psoriatic arthritis (PsA).

Patients and methods. The study included adult patients (age ≥18) with active PsA, bionaive or previously treated with bDMARDs. Comparison technologies included: adalimumab (ADA), guselcumab, golimumab, ixekizumab, secukinumab (SEC), tofacitinib (TOFA), certolizumab pegol (CZP), upadacitinib (UPA), ustekinumab, etanercept. The efficacy and safety of the bDMARDs and tsDMARDs included in the study were evaluated based on the results of a systematic search and analysis of data on the comparative clinical efficacy and safety of their use. First of all, the results of phase III randomized controlled trials of drugs that are used to treat active PsA in adult patients as active treatment compared with placebo or with another active drug, or systematic reviews with meta-analysis (MA) and network MA based on them, were considered. The period from the 12th to the 24th week after the start of therapy was taken as the time point for assessing the clinical efficacy of drugs, and the frequency of achieving the ACR20/50/70 criteria was taken as the performance indicator. Cost per responder (СpR), calculated on the basis of the cost of PsA therapy by the time a response is achieved according to the ACR20/50/70 criteria, was used as a criterion for clinical and economic efficiency and to analyze the impact on the budget.

Results and discussion. The data of the performed MA indicate a significantly greater effectiveness of the analyzed bDMARDs and JAKi compared to placebo in terms of the frequency of achieving a response according to the ACR20/50/70 criteria both in the group of bionaive patients and in the group of PsA patients, previously treated with bDMARDs. There were no differences between the drugs included in the study in terms of the frequency of achieving ACR20/50/70 response during the treatment of PsA. According to the study, by the 24th week of therapy, ADA, UPA and SEC 150 mg were characterized by the lowest costs to achieve the ACR20/50/70 criteria in bionaive patients and ACR20/50 in patients who were previously treated with bDMARDs. A low CpR value was determined in cases of ADA 40 mg and UPA 15 mg use for the treatment of patients with PsA who had not previously received bDMARDs. Among interleukin inhibitors, the lowest CpR value was registered for SEC 150 mg. By the 12th week of treatment, the CpR of TOFA 5 mg was higher compared to that of UPA 15 mg. CpR indicators for achieving ACR20/50 criteria in patients who were previously treated with bDMARDs were lower in UPA 15 mg and CZP compared to other drugs.

Conclusion. The results of the study demonstrate the clinical and economic feasibility of introducing different bDMARDs and JAKi into real practice of PsA treatment. At the same time, the use of original drugs is not always associated with significant costs per 1 patient who responded to treatment. In the absence of direct comparisons, real clinical practice provides important information about the relative efficacy and safety of alternative therapies in the management of PsA patients.

Lack of highly sensitive and specific methods of laboratory and instrumental diagnostics leads to difficulties in timely verification of Takayasu's arteritis (AT).

Objective: to analyze the clinical course, laboratory and instrumental markers of vascular inflammation in the Kyrgyz cohort of patients with AT.

Patients and methods. The study included 75 patients with a reliable diagnosis of AT, who were hospitalized and observed on an outpatient basis at the clinic of the National Center for Cardiology and Therapy named after acad. Mirsaida Mirrakhimova from January 2011 to April 2022. Patients were examined using clinical, laboratory and instrumental methods once every 2 years. The follow-up period was 1–5 years in 45 (60%) patients and 6–15 years in the remaining 30 (40%) patients. All patients underwent a clinical and standard laboratory work-up with CRP and interleukin 6 levels assessment, as well as ultrasound Dopplerography of peripheral arteries in the color Doppler mapping mode and multislice computed tomography-panaortography.

Results and discussion. Lesions of the common carotid (85.33%) and subclavian (84%) arteries were detected more often. Involvement of the abdominal aorta was noted in 60% of patients and was accompanied by stenosis of the renal arteries in 100% of cases. The clinical picture of the disease was mainly represented by cardiac pathology in the form of arterial hypertension (84%) and aortic regurgitation (68%) with the development of decompensated chronic heart failure in 15% of patients. During the dynamic observation, significant improvement in the course of the disease, clinical symptoms, decrease in the severity of vascular changes were not revealed, with the exception of a decrease in the clinical activity of AT (p<0.05) in one third of patients (37.4%). Conclusion. The severity of clinical manifestations and the course of AT in the Kyrgyz cohort was due to cardiovascular pathology. As dynamic observation showed, the lack of significant improvement in the course of the disease was largely due to the long duration of chronic inflammation, late diagnosis, development of irreversible stenotic, occlusive and aneurysmal changes, as well as the fact that patients did not receive adequate pathogenetic therapy at the onset of the disease. Keywords: <0.05) in one third of patients (37.4%).

Conclusion. The severity of clinical manifestations and the course of AT in the Kyrgyz cohort was due to cardiovascular pathology. As dynamic observation showed, the lack of significant improvement in the course of the disease was largely due to the long duration of chronic inflammation, late diagnosis, development of irreversible stenotic, occlusive and aneurysmal changes, as well as the fact that patients did not receive adequate pathogenetic therapy at the onset of the disease.

Objective: to describe musculoskeletal immune-mediated adverse events (iAEs) associated with the therapy of solid tumors with immune checkpoint inhibitors (ICIs, inhibitors of the PD-1/PD-L1 pathway).

Patients and methods. 13 patients receiving ICIs therapy with musculoskeletal iAEs were examined. The average age of patients was 59±10 years. All cases had a histologically verified diagnosis of a malignant solid neoplasm: melanoma (n=5), kidney cancer (n=3), bladder cancer (n=2), non-small cell lung cancer (n=1), breast cancer (n=1), cervical cancer (n=1). All patients were prescribed inhibitors of the PD-1/PD-L1 signaling pathway: nivolumab (n=6), pembrolizumab (n=3), atezolizumab (n=3), prolgolimab (n=1). In 7 (54%) patients, in addition to musculoskeletal disorders, other AEs were also detected: thyroiditis (n=3), neuropathy (n=2), rash (n=1), dry syndrome (n=1), hepatitis (n=1). The median time from the start of antitumor immunotherapy (IT) to the onset of musculoskeletal pathology was 20 [9; 48] weeks.

Results and discussion. Clinical manifestations of musculoskeletal pathology included: synovitis in 9 (69%) patients, tenosynovitis in 11 (85%), enthesitis in 4 (31%), morning stiffness in the joints for more than 30 minutes in 4 (31%). In 11 cases, musculoskeletal pathology was persistent (in 9 patients with arthritis and 2 with periarthritis) and in 2 – transient. The knee (77%), shoulder (69%) and hand (54%) joints were most frequently affected, with bilateral involvement in 9 (69%) patients. Inflammatory changes in the joints were represented by mono- (n=1), oligo- (n=3) and polyarthritis (n=5), including those involving the small joints of the hands and/or feet (n=5) and predominantly affecting the joints of the lower limbs (n=3). In 3 patients with arthritis, periarticular changes dominated in clinical picture (in 2 patients with symmetrical polyarthritis and severe tenosynovitis, in another 1 patient – with RS3PE syndrome). The severity of musculoskeletal pathology was assessed using the CTCAE v5.0 toxicity criteria: grade 1 was documented in 2 (15.5%), grade 2 in 9 (69%), and grade 3 in 2 (15, 5%) patients. Laboratory workup revealed elevation of ESR ≥30 mm/h (median – 34 [14; 42] mm/h) in 7 out of 12 (58%) patients, elevation of CRP level >5 mg/l (median – 7.2 [4.6; 12.9] mg/l) – in 7 out of 10 (70%). In 7 out of 10 patients, antinuclear antibodies (Hep2) were detected in titers: 1:160 (n=2), 1:320 (n=3), 1:640 (n=2). Rheumatoid factor and antibodies to cyclic citrullinated peptide were not detected in any case. Therapy for musculoskeletal AEs included non-steroidal anti-inflammatory drugs (n=10), oral systemic glucocorticoids – GC (n=5), methotrexate – MT (n=1) and hydroxychloroquine (n=5), intra-articular administration of GC (n=1). Five patients with arthritis required long-term therapy (median duration – 12 [3; 12] months), in 1 patient with polyarthritis and severe tenosynovitis, antitumor IT was interrupted for the duration of the course of MTX treatment.

Conclusion. It has been shown that musculoskeletal iAEs have heterogeneous manifestations and may require long-term treatment and in rare cases, anticancer therapy interruption. Additional studies and close cooperation between rheumatologists and oncologists are needed to obtain a more complete understanding of the nature and spectrum of musculoskeletal AEs, to identify their clinical, laboratory and instrumental features, and to develop an management of patients algorithm.

Objective: to evaluate physical activity (PA) and its relationship with body composition in patients with rheumatoid arthritis (RA).

Patients and methods. The study included 93 women with RA. A standardized questionnaire survey, anthropometric measurements, laboratory work up, and dual-energy x-ray absorptiometry were conducted to assess body composition and bone mineral density. The level of PA was determined using the International Physical Activity Questionnaire (IPAQ).

Results and discussion. The IPAQ survey showed that 46 (49.5%), 41 (44.1%) and 6 (6.4%) patients had high, moderate and low levels of PA, respectively. The patients did not differ in clinical and anamnestic, laboratory and instrumental data depending on the level of PA. Correlations were found between total energy expenditure by IPAQ and daily food calcium intake (r=0.26, p=0.012), shoulder circumference (r=0.22, p=0.042) and postmenopausal duration (r=-0.27, p=0.016). The relationship between the sarcopenic phenotype (SP) and the time of vigorous physical activity less than 15 minutes per day was revealed (odds ratio, OR 6.31; 95% confidence interval, CI 1.75–22.71; p=0.004), between the frequency of moderate physical exercise and walking less than 4 times a week (OR 4.09; 95% CI 1.16–14.47; p=0.027 and OR 4.73; 95% CI 1.24–18.07; p=0.021, respectively), the presence of osteoporosis – OD (OR 9.41; 95% CI 2.73–32.47; p <0.001). The risk of obesity increased with vigorous exercise less than 15 minutes per day (OR 3.03; 95% CI 1.11–8.29; p=0.029). The osteoporotic phenotype (OPP) was associated with patient age (OR 1.12; 95% CI 1.05–1.19; p=0.001) and the presence of SP (OR 8.97; 95% CI 2.39– 33.60; p=0.001).

Conclusion. Half of the patients had moderate and low level of PA, independent of age, RA duration and activity. SP was associated with insufficient PA and the presence of OPP. Obesity is also associated with lack of PA, while OPP is associated with age and the presence of SP.

Objective: to study the dynamics of back pain severity and the frequency of its individual components, characterizing the inflammatory and mechanical rhythm, on the background of gestation in women with ankylosing spondylitis (AS) and compare them with manifestations of dorsopathy in healthy pregnant women; to determine the information value of BASDAI during pregnancy, i.e. to identify its components with the optimal sensitivity and specificity ratio for assessing AS activity during gestation.

Patients and methods. The main group consisted of 49 pregnant women with AS who met the modified New York criteria of 1984. The average age of patients was 31.7±4.9 years, the average duration of the disease was 134.4±85.8 months. BASDAI for trimesters of pregnancy was: 2.3 [1.2; 4.4], 2.8 [1.4; 4.2] and 2.2 [1.6; 4.0]. The control group included 51 pregnant women with back pain associated with gestation, without rheumatic diseases. The average age was 28.0±4.4 years. The intensity of back pain was assessed on a numerical rating scale. ROC-analysis was performed with calculation of the area under the curve (AUC) of each component of BASDAI in each pregnancy trimester.

Results and discussion. More than 80% of pregnant women with AS experienced back pain, while the intensity of general back pain did not differ from that in the control group. Night back pain with improvement on awakening in the main group was present in 70%, 58% and 68.8% of women, respectively, in the I-III trimesters; its intensity was 3 [1; 5], 3.5 [3; 6] and 3.4 [2; 5] respectively; the frequency and severity of night pain were higher than in the control group. The number of women with improvement after exercise in the II and III trimesters did not differ in both groups. In the second half of pregnancy, 40% of AS patients noted improvement during rest, 52.1% – increased pain after exercise; the frequency of mechanical rhythm pain elements remained lower than in the control group. The AUC value for BASDAI in the first trimester was 0.74; AUC of all BASDAI components was >0.5. In the II and III trimesters, the AUC values for fatigue and back pain were 0.8.

Conclusion. During pregnancy the vast majority of women with AS experience back pain, the nature of which changes in the second half of gestation. Night pain that improves on awakening reflects AS activity and is not related to pregnancy. The BASDAI components of severity and duration of morning stiffness have the highest classification value during pregnancy.

The COVID-19 pandemic is a global health emergency. The relevance of this problem in immunoinflammatory rheumatic diseases is due to the increased risk of infection with SARS-CoV-2 and its severe course. The paper describes the clinical features and morphological changes in organs in a patient with rheumatoid arthritis and secondary amyloidosis of the heart and kidneys, who died from an infection caused by SARS-CoV-2.

Epstein-Barr virus (EBV) belongs to the family of herpesviruses (herpes type 4) and is one of the most common and highly contagious. During the pandemic of a new coronavirus disease, it was found that in patients previously infected with EBV, COVID-19 can cause its reactivation, which is often manifested by the clinic of acute hepatitis. The article presents a clinical case of the development of acute hepatitis in a patient with mixed infection with EBV and SARS-CoV-2 in combination with allergic toxic reaction while taking sulfasalazine prescribed for spondyloarthritis. A feature of this case was the development of severe hepatitis of mixed genesis with a favorable outcome. The importance of adherence to drug monitoring rules for newly prescribed drugs for COVID-19 was emphasized. In severe cases of the disease, the possibility of mixed infection should be taken into account.

Infections and systemic vasculitis (SV) are characterized by mutual influence, which increases the risk of occurrence, aggravates the course and outcome of the disease. The review considers the issues related to both the trigger role of infections in the development of SV and comorbid infections (CI) that complicate the course of the disease. Recognition of the infectious etiology of SV is of great importance, since it requires a comprehensive examination and, if necessary, early and complete etiotropic treatment. Since SV per se and the use of both induction and maintenance immunosuppressive therapy are significant risk factors for secondary CIs, special attention should be paid to the prevention of the latter, including vaccination, primarily against influenza and pneumococcal infections.

The review is devoted to the relationship between the pathogenetic mechanisms of coronavirus infection (COVID-19) and immunoinflammatory rheumatic diseases (IRD). The current knowledge on the pathogenesis of COVID-19 is summarized, including the mechanisms of coagulopathy, hyperproduction of pro-inflammatory cytokines, and antiphospholipid antibodies that are common with IRD. The presence and clinical significance of detection of various autoantibodies in COVID-19, which probably play a pathogenetic role in immune dysregulation, were analyzed. Based on the data of recent studies, risk factors and features of the severe course of infection in patients with IRD are considered.

Periarticular soft tissue disorders (PSTD) are typical manifestation of immunoinflammatory rheumatic diseases, primarily spondyloarthritis. However, in real clinical practice, physicians involved in the management of patients with musculoskeletal diseases often have to deal with "non-systemic" PSTD resulting from trauma, physical exertion, or degenerative processes associated with endocrine, metabolic, and cardiovascular diseases. PSTD causes acute and chronic pain, significant impairment of function and deterioration in the quality of life. The treatment of this pathology is complex and includes non-drug methods, painkillers and local injection therapy. Hyaluronic acid (HA) drugs occupy an important place in this treatment. Their use is pathogenetically justified, because when the tendon and enthesis are involved, the internal environment (intercellular matrix) change, and its basis is natural hyaluronate, which provides the viscoelastic properties of biological structures, as well as regulates metabolism, proliferative and immune processes. A relatively low molecular weight HA drug (530–730 kDa) has favorable rheological parameters, anti-inflammatory and anabolic potential, which makes it the drug of choice for local injection therapy of PSTD. This review briefly presents data on the pathogenesis of PSTD and the advisability of HA drugs use for its therapy, as well as the evidence base for the use of HA (530–730 kDa) in various types of ligamentous apparatus lesions.

Back pain can be caused by various etiological factors, and its development is mediated by various pathogenetic mechanisms. Anatomical structures that can participate in the formation of pain include muscles, fascia, ligaments, tendons, facet joints, intervertebral discs and vertebrae. Changes in the central pain modulation system are an important factor in the development of chronic low back pain (LBP). Accumulating evidence allows us to consider LBP not as a series of isolated unrelated episodes, but as a long-term condition with a variable course. In the practice of a rheumatologist, LBP can occur as a manifestation of the underlying disease or as a comorbid pathology on the background of rheumatic pathology. In this case, it may be difficult to determine the activity of the underlying disease and the effectiveness of the therapy.

Control of chronic pain is one of the main elements of the complex therapy of rheumatic diseases (RD). The use of analgesics is of fundamental importance for the management of patients with osteoarthritis (OA), since a unified system of pathogenetic therapy has not yet been developed for this disease. In immunoinflammatory rheumatic diseases (IRDs), such as rheumatoid arthritis, effective pathogenetic therapy can successfully control inflammatory activity. However, in many cases, in patients with IRDs, unpleasant symptoms (pain, fatigue, poor general well-being, etc.) persist even during remission and low inflammatory activity. This is associated with persistent structural changes, “secondary” OA, central sensitization, and concomitant fibromyalgia. Therefore, approximately 50% of patients with IRDs receiving modern pathogenetic therapy require additional use of analgesics. Therapy for musculoskeletal pain in RD should be complex, include drugs with different mechanisms of action and non-drug methods. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line therapy, they have good analgesic and anti-inflammatory potential. The choice of a specific NSAID should be based on an individual assessment of the clinical situation and the presence of risk factors for possible complications. Among NSAIDs, aceclofenac should be singled out – an effective drug with a favorable safety profile, which is confirmed by a large number of clinical studies and real clinical practice.

In the treatment of joint diseases, including osteoarthritis (OA), the use of standardized extracts of undenatured type II collagen (UDC-II) is promising. It is known that UDC-II is involved in the regulation of innate and adaptive immunity (reduction of autoimmune reactions that stimulate cartilage degradation) and in the reduction of chronic inflammation activity (modulation of cytokines and prostaglandins). The effect of UDC-II on discoidin receptors of chondrocytes helps to prevent structural disorders of the cartilage connective tissue. Experimental and clinical studies have shown that under the influence of standardized UDC-II, there is an increase in the proportion of regulatory CD4+ T cells, a decrease in the levels of pro-inflammatory cytokines, such as interleukin (IL) 1β, IL6, tumor necrosis factor α, CRP, prostaglandins in the blood, as well as matrix metalloproteinase 3 and NF-κB expression in cartilage. The use of UDC-II in OA leads to a significant reduction in pain, an increase in the range of joint motion, an improvement in joint function according to WOMAC and quality of life.